As is known, the minor alkaloids of Vinca rosea L. with diindole skeletons possess valuable cytostatic effects (U.S. Pat. Nos. 3,097,137 and 3,205,22; Hungarian Patent specifications Nos. 153,200; 154,715 and 160,967.) Of these minor alkaloids, vincristine is the one regarded to be the most valuable, making up some hundredths of a percent of the total alkaloid content, whereas the less effective vinblastine and vinleurosine are present in an amount of about 1 to 2 percent of the total alkaloid content.
In the recent past, the demand for the latter two alkaloids has increased considerably, which can be attributed to the recognitions that vinblastine can be converted into the more valuable vincristine by a semisynthetic process (Hungarian Patent specification No. 165,599), and that the N-formyl derivative of vinleurosine (Hungarian Patent specification No. 165,986) also inhibits the growth of tumors resistant towards the cytostatic agents known before.
The more recent investigations in this field have been directed to the preparation of further effective semisynthetic alkaloid derivatives, such as the carboxamide and deacetyl derivatives (published German patent applications Nos. 1,795,763 and 2,415,890), as well as on the isolation of further minor alkaloids, such as vincadioline, leurocolombine (U.S. Patent Nos. 3,887,565 and 3,890,325) and 4-deacetoxy-vinblastine [N. Neuss, A. J. Barnes and L. L. Huckstep: Experimentia 31/1, (18-19)].
The isolation of the further minor alkaloids was rendered possible by the improvements in chromatographic techniques, more particularly, by the use of high-pressure chromatographs. Using such equipment, even compounds with rather similar physical constants, such as the retention factor--R.sub.f, and chemical structures can be separated successfully from each other. Nowadays high-pressure chromatographs can be applied successfully for laboratory scale operations; their utilization is, however, extremely complicated and expensive in large-scale techniques.
N. Neuss et al. [Experimentia 31/1, 18-19(1975)] succeeded in isolating 4-deacetoxy-vinblastine, an accompanying alkaloid of vinblastine not known before, by subjecting vinblastine to two chromatographical separations and two recrystallizations. The U.V. and I.R. spectra of vinblastine and 4-deacetoxy-vinblastine are very closely related, and the difference between their retention factors R.sub.f amounts to only 0.03. In the cited publication, the authors described the separation technique for the two alkaloids and the difficulties, which had arisen in connection with their structure determinations. They did not give, however, any information on the pharmacological or other properties or effects of the new alkaloid.